Rbpj expression in regulatory T cells is critical for restraining T_H2 responses

The transcriptional regulator Rbpj is involved in T-helper (T_H) subset polarization, but its function in T_reg cells remains unclear. Here we show that T_reg-specific Rbpj deletion leads to splenomegaly and lymphadenopathy despite increased numbers of T_reg cells with a polyclonal TCR repertoire. A specific defect of Rbpj-deficient T_reg cells in controlling T_H2 polarization and B cell responses is observed, leading to the spontaneous formation of germinal centers and a T_H2-associated immunoglobulin class switch. The observed phenotype is environment-dependent and can be induced by infection with parasitic nematodes. Rbpj-deficient T_reg cells adopt open chromatin landscapes and gene expression profiles reminiscent of tissue-derived T_H2-polarized T_reg cells, with a prevailing signature of the transcription factor Gata-3. Taken together, our study suggests that T_reg cells require Rbpj to specifically restrain T_H2 responses, including their own excessive T_H2-like differentiation potential.